Mass spectrometers have been known since the early experiments of J. J. Thomson who, with his "parabola" instrument, showed that a beam of ions having various masses and a range of energies can be mass-analyzed by passing them through uniform parallel magnetic and electric fields. These early experiments led to discoveries of previously unknown isotopes and to an increased understanding of ionization processes of atoms and molecules as well as various electron-mediated dissociation processes. As mass spectrometers have subsequently evolved, great increases have been made in the quality of these instruments, including in their resolving and detection powers.
Modern mass spectrometers are widely used for analysis of unknown mixtures of gases or liquids. They have also found wide applicability in detailed studies of chemical reaction mechanisms, such as analysis of free radicals and other reaction intermediates.
Since their debut, most mass spectrometers have employed at least one magnetic field for performing mass analysis. Such magnetic instruments are conventionally termed "sector" instruments.
Since the mid 1950s, mass analyzers employing only electric fields have been increasingly used, offering attractive features such as smaller size and lighter weight relative to the typically massive sector instruments. Electric-field instruments have exhibited a capability of scanning a range of masses at high repetitive rates, which has provided valuable data in studies of fast chemical reactions. Examples of such instruments include the "quadrupole mass filter" and the "ion trap."
A large amount of research using various types of mass spectrometers has been performed by analyzing positive ions produced by bombarding target molecules using "fast" electrons (i.e., electrons having a relatively high kinetic energy, greater than 10 to about 30 eV or higher). Briefly, according to conventional methods known in the art, the fast electrons are produced by a hot filament under high vacuum. The electrons are focused magnetically into a beam and urged into an "ionization chamber," also under high vacuum, containing molecules of the target material to be analyzed. Impingement of the fast electrons with molecules of the target material causes the target molecules to fracture into a number of positively charged molecular fragments having different m/z values. The positive ions are then drawn into the mass analyzer for analysis.
Positive-ion mass spectrometry (PIMS) using conventional methods and apparatuses has certain disadvantages. One disadvantage is that the positive ions (cations) are molecular fragments produced by fast electrons. Also, filaments of the type conventionally used with mass spectrometers produce electrons having a relatively broad range of individual kinetic energies (at least several electron volts). As a result, a number of differently sized cationic fragments of the molecules are formed. With a complex sample, the large number of cationic fragments that is generated produces a complex spectrograph that can be difficult to interpret.
Conventional mass spectrometers allow the operator to adjust the electron energy. (This is one way in which specificity can be enhanced because different compounds have different ionization energies and adjusting the electron energy can result in preferential ionization of a particular class of compounds relative to another class of compounds in a sample.) However, adjusting the electron energy in this manner does not result in a narrowing of the spectrum of electron energy produced by the filament; it merely results in a shifting up or down of the median energy of electrons produced by the filament. As a result, it is very difficult with such instruments to achieve truly energy-selective ionizations.
Conventional negative-ion mass spectrometry (NIMS) overcomes certain disadvantages of conventional PIMS. In NIMS, the ions that are mass-analyzed are anions, not cations. The anions are typically produced employing electrons having a lower kinetic energy (i e., "slow" electrons which have energies of about 10 eV or less) than the electrons usually employed in conventional PIMS. Impingement of a slow electron with a target molecule can result in "capture" of the electron by the target molecule. Target molecules of many types of compounds remain intact as molecular anions after capturing electrons rather than breaking apart into cationic fragments, particularly if, for each such target molecule, the energy of the impinging electron is substantially equal to a resonance energy of the target molecule. Electrophilic target molecules are especially likely to undergo such resonant electron capture.
Another type of electron capture, termed "dissociative electron capture" results in a relatively limited splitting of the target molecule, such as the removal of one or more particular substituent groups, to produce at least one type of anionic fragment. Specifically which type of dissociation that occurs is dependent in part upon the energy of the impinging electron. (These technologies are conventionally termed "electron-capture negative-ion mass spectrometry" or ECNIMS.)
In conventional ECNIMS, the spectrograms are generally simpler than spectrograms in conventional PIMS. As a result, it can be easier in ECNIMS to discern the presence of a particular compound in the spectrogram. Thus, ECNIMS can allow identification of compounds present at low concentrations in complex mixtures that would be difficult to analyze using PIMS.
In conventional ECNIMS, the requisite "slow" electrons are generated by passing a beam of "fast" electrons produced by a hot filament into a "buffer" gas in an ionization chamber which also contains molecules of the sample to be mass-analyzed. As the fast electrons impinge upon molecules of the buffer gas, much of the kinetic energy of the electrons is dissipated. In order to achieve sufficient slowing of most of the electrons before they encounter molecules of the sample, a high molecular density of the buffer gas relative to the molecular density of the sample in the ionization chamber is required.
The following are representative reactions of the buffer gas with fast electrons (wherein "Bu" designates a molecule of the buffer gas and "M" designates a molecule of the target compound to be mass-analyzed): EQU Bu+e.sub.fast.sup.- .fwdarw.Bu.sup.+.+e.sub.slow.sup.- +e.sub.fast.sup.- EQU e.sub.slow.sup.- +M.fwdarw.M.sup.-.
Unfortunately, the presence of a large number of molecules of the buffer gas relative to the molecules of the target compound can result in reactions in which the negative ions of the sample compound (M.sup.-.) are reverted back to uncharged species before the negative ions can exit the ionization chamber and enter the mass analyzer: EQU Bu.sup.+.+M.sup.-..fwdarw.Bu+M
It is also possible for some of the fast electrons entering the ionization chamber to encounter molecules of the target compound before becoming sufficiently slowed, thereby producing undesirable positive ions. The presence of such neutral species and other spurious reaction products (including undesirable positive-ion products) can seriously degrade resolution and make the resulting mass spectrograms difficult to interpret.
Another disadvantage with conventional ECNIMS is that electrons tend to repel each other and the degree of such repulsion is more pronounced with slow electrons than with fast electrons. Such repulsion can cause substantial spreading of a beam of slow electrons, which can severely limit beam intensity. The lower the electron energy, the more pronounced the repulsion, which can unacceptably limit sensitivity and resolving power of a NIMS instrument.
In addition, the high buffer-gas pressure required in the ionization chamber is much too high for many types of mass analyzers. For example, with the conventional buffer gas methane (CH.sub.4), the pressure in the ionization chamber must be about 0.5 to 1 Torr, compared to a typical "vacuum" of at least about 10.sup.-5 to 10.sup.-6 Torr that must be maintained in the downstream mass analyzer during actual use. As a result, conventional ECNIMS work requires that large-capacity (and therefore heavy and bulky) vacuum pumps be employed in order to achieve the requisite lowering of pressure in the mass analyzer, relative to the pressure in the ionization chamber, at the requisite rate. Such large pumping capacity has virtually prevented ECNIMS from being used in locations other than in a laboratory where large, heavy vacuum pumps that consume large amounts of energy can be accommodated. Also, the buffer-gas pressures required to adequately slow electrons are incompatible with the vacuum and electrical requirements necessary to isolate 25 KeV at 1 MHz which are necessary for operation of an ion trap. In addition, conventional ECNIMS requires a supply of the buffer gas which is usually supplied from a cumbersome and potentially dangerous gas cylinder.
To meet modern demands of environmental monitoring, surveillance, and other sophisticated uses, it is often necessary for the analytical equipment to be used on-site, such as in the field or away from a laboratory. This is particularly important when the sampled materials cannot practicably be removed to a laboratory for analysis or the target compound is simply too evanescent to permit anything other than real-time monitoring. Although ECNIMS has a sensitivity to be of significant value in many such applications, its use is often precluded because of the current necessity to maintain such instruments in a laboratory setting.
Another disadvantage of conventional ECNIMS instruments is their general inability to produce reproducible mass spectral data. Buffer gases such as methane tend to produce polymeric materials under ECNIMS conditions that coat the ion source and require frequent cleaning.
Therefore, there is a need for methods that are capable of accurately detecting the presence in samples of subject analytes at extremely low concentrations as required in environmental monitoring, forensic analysis, drugs and explosives detection, and other applications requiring high detection sensitivity and accuracy.
There is also a need for such methods capable of distinguishing between isomers of a particular subject analyte.